During the Canadian Cardiovascular Society's recent congress in Vancouver, Dr. Arnold Strauss provided a series of vignettes to demonstrate the role of molecular pathogenesis in congenital heart disease. Strauss, a pediatric cardiologist and molecular biologist at Washington University in St. Louis, used DiGeorge syndrome to indicate how a complex abnormality on chromosome 22q11 produces multiple cardiac abnormalities, including truncus arteriosus, tetralogy of Fallot and pulmonary atresia.

This abnormality is also associated with absence of the thymus gland, perturbations in calcium homeostasis and T-cell deficiency. Taken together, these lead to increased susceptibility to infection. Behavioural problems involving psychoses and other psychiatric disturbances occur frequently in patients with this genetic condition.

Strauss said these types of diseases are forcing doctors to think more broadly about patients with heart disease. For instance, pediatric cardiologists have traditionally focused on anatomic diagnoses limited to the cardiovascular system. However, the DiGeorge syndrome is associated with multiple system defects that cross medical disciplines, thus requiring flexibility, lateral thought and a more generalized approach to the patient. Another example of this is the phenotype caused by mutations in the TBX5 gene. Affected patients often exhibit atrial septal defect, and there may be associated abnormalities of the tricuspid valve and a ventricular septal defect, as well as developmental skeletal abnormalities. This molecular information may provide an explanation for some cases of sporadic congenital heart disease and may enhance physicians' ability to make diagnoses.

The theme running through all of these vignettes was Strauss's idea that physicians must begin to think more as developmental biologists and less as technicians who simply focus on anatomic abnormalities of the heart. Indeed, patients with the same apparent anatomic defects may have substantial clinical differences, and the consequences of abnormalities both within and outside the cardiovascular system need to be integrated into their overall care. — Dr. Paul Armstrong, an Edmonton cardiologist, and Dr. Robert Hegele, who cochaired a symposium at the congress, wrote this article; physicians interested in submitting similar reports should contact John Hoey, 800 663-7336 x2118; [email protected].